STUDY: CARBON DIOXIDE MAY
FIND NEW USE IN PRODUCING MEDICAL IMPLANTS

COLUMBUS, Ohio – Carbon dioxide, an environmentally friendly solvent
for dyeing and dry cleaning, may become a valuable new tool for making
medical implants, according to a study at Ohio State University.

David
Tomasko

Engineers here used compressed carbon dioxide (CO2) to push chemicals
into a plastic that is often used as a bone replacement. With further
development, the technology could be used in a wide range of plastics
that release medicines -- from antibiotics to anti-tumor agents -–
into the body.

The high-pressure, high-temperature CO2 is neither gas nor liquid, but
is known as a “supercritical fluid,” explained David
Tomasko, associate professor of chemical
engineering at Ohio State. Supercritical fluids are often used in
industry because they penetrate materials like a gas but can dissolve
some substances -- such as grease -- and other chemicals like a liquid.

“Though supercritical CO2 has long been developed as a means of
extracting molecules, this work shows that it can be used in the opposite
way,” said David Tomasko, associate professor of chemical engineering
at Ohio State.

For the next step in
this research, the engineers will be working with biodegradable
plastics and determine whether the medicine remains effective after
being embedded with the supercritical fluid.

The study also revealed that engineers can control the pressure of the
CO2 to alter the internal structure of the plastic and create voids that
may enable the material to hold larger quantities of medicine than might
normally be possible.

Tomasko and John Lannutti, associate professor of materials science
and engineering, their graduate students Taryn Sproule and Hongbo Li,
and undergraduate student J. Alex Lee, published their results in a recent
issue of the Journal
of Supercritical Fluids.

Supercritical CO2 is gaining popularity as an environmentally friendly
dry-cleaning agent and textile-dyeing solvent, but it is the fluid’s
ability to sterilize surfaces that could prove key for making medically
active implants. Currently, implants are sterilized with heat, radiation,
or chemicals that can make embedded medicines less effective, Tomasko
explained.

The engineers’ early tests with a protein solution suggest that
supercritical CO2 may leave medicines intact.

They applied a coating of the protein solution onto dime-sized plastic
disks with a cotton swab, and placed the disks in a glass tank, which
they then filled with supercritical CO2. The proteins contained a fluorescent
biomarker, so the researchers were able to track how well the proteins
penetrated the plastic by examining cross-sections of the material under
a microscope in ultraviolet light.

The microscope showed that the proteins survived the embedding process,
and formed a layer 30 micrometers, or millionths of a meter, beneath the
surface of the plastic.

Although the plastic -- polymethylmethacrylate, or PMMA -- was undamaged
by the procedure, the interior of the disks foamed up into a Swiss cheese-like
texture, with voids opening inside. The faster the engineers turned off
the high-pressure CO2, the foamier the material became. Lowering the pressure
slowly had the opposite effect.

Tomasko envisions that such voids within an implant could come in handy
for holding extra quantities of a drug for long-term therapy.

Today, medical implants are used for mechanical support where tissue
or bone has been removed. The researchers’ vision is to “piggyback”
drug delivery onto this mechanical function. The implant may be impregnated
with drugs to prevent inflammation or infection following surgery. Or,
in cases where a patient has had bone surgically removed as part of a
treatment for cancer, doctors may also need to dispense anti-tumor agents
from the implant for a longer period, Tomasko explained.

He’s been working with David Powell, clinical assistant professor
of otolaryngology, to investigate the potential use of such implants for
patients who’ve had facial surgery.

Since completing their initial study, the engineers have begun using
a porous glass disk to dispense protein solution onto the PMMA, instead
of a cotton swab. Still, they found that the proteins don’t penetrate
the PMMA evenly, but form clumps instead -- an effect Tomasko suspects
is due to the tightly packed polymer chains that make up the plastic.

“We think the CO2 lubricates the polymer chains so the protein
molecules can slip in-between,” he said.

For the next step in this research, the engineers will be working with
biodegradable plastics and determine whether the medicine remains effective
after being embedded with the supercritical fluid.

Douglas Kniss, professor of obstetrics and gynecology at Ohio State,
provided the protein solution, and Kathy Wolken, senior electron microscopist
at the Campus Microscopy and Imaging Facility, assisted with the imaging
of the PMMA samples.